Post-transplant Pembrolizumab May Delay Immune Reconstitution for Patients With DLBCL

Patients with diffuse large B-cell lymphoma (DLBCL) who received pembrolizumab as maintenance therapy following an autologous stem cell transplantation (ACST) experienced a delay of at least 18 months in the reconstitution of their CD19+ cells, according to a flow cytometry study which included data on patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (CHL) and DLBCL participants in a previously-reported phase 2 trial.

All of the patients with DLBCL received anti-CD20 monoclonal antibody therapy before transplant. No other differences in immune reconstitution based on lymphoma subtype were observed.

“Whereas the clinical benefit of ASCT has traditionally been attributed solely to cytoreduction from intensive chemotherapy, ASCT has important immunogenic effects that may contribute to its antitumor efficacy and could provide a favorable immune environment for post-ASCT immune-based maintenance treatments. Our study suggests that early features of post-ASCT immune reconstitution could be associated with progression-free survival (PFS) and the risk of immune-related adverse events (irAEs) and warrant additional investigation,” wrote Reid Merryman, MD, Dana-Farber Cancer Institute, Boston, and co-authors.

Thus, researchers collected post-ASCT peripheral blood samples from 59 patients who received pembrolizumab in the phase 2 study, used a panel of fluorophore-conjugated monoclonal antibodies to identify B-cells, natural killer (NK) cells, various dendritic cells, and T-cell subsets, and compared the results to 85 blood samples from a control group that received ASCT, but which did not participate in the phase 2 trial and did not receive pembrolizumab.

The researchers also conducted an exploratory analysis, which indicated that a higher baseline CD4+ terminal effector memory cell count (defined as CD3+CD4+CD45RA+CD62L-) was associated with an inferior PFS among those who received pembrolizumab maintenance (P = .003).

Additionally, lower absolute levels of NK cells (P = .009), PD-1+ CD4+ T cells (P = .005), and PD-1+ CD8+ T cells (P = .005) before pembrolizumab initiation were each associated with a higher risk of grade 2+ irAEs.

Source:
Merryman R, Redd R, Jeter E, et al. Immune Reconstitution following High-Dose Chemotherapy and Autologous Stem Cell Transplantation with or without Pembrolizumab Maintenance Therapy in Patients with Lymphoma. Transplant Cell Ther. Published online October 17, 2021. doi:10.1016/j.jtct.2021.10.010.